Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer

EGFRmutations define a subset of lung cancers associated with sensitivity to the kinase inhibitors gefitinib and erlotinib. However, primary and acquired resistance remains a major clinical problem. This article reviews recent advances towards biologically based rational treatment of this disease. Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) was first recognized in 2004 as a distinct, clinically relevant molecular subset of lung cancer. The disease has been the subject of intensive research at both the basic scientific and clinical levels, becoming a paradigm for how to understand and treat oncogene-driven carcinomas. Although patients with EGFR-mutant tumours have increased sensitivity to tyrosine kinase inhibitors (TKIs), primary and acquired resistance to these agents remains a major clinical problem. This Review summarizes recent developments aimed at treating and ultimately curing the disease.